1rjx
From Proteopedia
Revision as of 04:35, 3 May 2008
Human PLASMINOGEN CATALYTIC DOMAIN, K698M MUTANT
Contents |
Overview
Streptokinase (SK) is a human plasminogen (Pg) activator secreted by streptococci. The activation mechanism of SK differs from that of physiological Pg activators in that SK is not a protease and cannot proteolytically activate Pg. Instead, it forms a tight complex with Pg that proteolytically activates other Pg molecules. The residue Lys-698 of human Pg was hypothesized to participate in triggering activation in the SK-Pg complex. Here, we report a study of the Lys-698 to Met substitution in the catalytic domain of Pg (microPg) containing the proteolytic activation-resistant background (R561A). While it remains competent in forming a complex with SK, maintaining a comparable equilibration dissociation constant (K(D)), the recombinant protein shows a nearly 60-fold reduction in amidolytic activity relative to its R561A background when mixed with native SK. A 2.3 A crystal structure of this mutant microPg confirmed the correct folding of this recombinant protein. Combined with other biochemical data, these results support the premise that Lys-698 of human Pg plays a functional role in the so-called N-terminal insertion activation mechanism by SK.
Disease
Known disease associated with this structure: Conjunctivitis, ligneous OMIM:[173350], Plasminogen Tochigi disease OMIM:[173350], Plasminogen deficiency, types I and II OMIM:[173350], Thrombophilia, dysplasminogenemic OMIM:[173350]
About this Structure
1RJX is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Characterization of Lys-698-to-Met substitution in human plasminogen catalytic domain., Terzyan S, Wakeham N, Zhai P, Rodgers K, Zhang XC, Proteins. 2004 Aug 1;56(2):277-84. PMID:15211511 Page seeded by OCA on Sat May 3 07:35:18 2008
